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Education, cognitive test scores, and black-white differences in dementia risk.

OBJECTIVES: To compare dementia risks of elderly black and white subjects and to determine whether differences in education and cognitive test scores contribute to the inconsistency in reported differences between these groups. DESIGN: Longitudinal, 6-year follow-up. PARTICIPANTS: Two thousand seven hundred eighty-six older black and white subjects in the Cardiovascular Health Study. MEASUREMENTS: Age, education (>10 years vs < or =10 years), Modified Mini-Mental State Examination score (3MS, < or =85 vs >85). Potential confounders were sex, depression, apolipoprotein E4 genotype, vascular disease, and baseline magnetic resonance imaging changes. RESULTS: White subjects with low education and black subjects with high education had twice the risk of dementia of white subjects with high education (95% confidence interval (CI)=1.5-2.4 and 95% CI=1.4-2.7); black subjects with low education had five times the risk of dementia (95% CI=3.4-7.7). Likewise, for subjects with low 3MSE scores, black subjects had 6.7 times the risk of dementia (95% CI=4.7-9.7) and white subjects had 2.7 times the risk of dementia (95% CI=2.2-3.5) as white subjects with high 3MSE scores. Finally, in Cox models, there was no significant black-white difference in dementia risk after adjustment for all confounders and baseline 3MSE. CONCLUSION: Black race was associated with greater dementia risk even after adjustment for education and other potential confounders. This black-white difference in dementia risk was markedly attenuated after adjustment for baseline cognitive screening scores. The apparent race effect may reflect gaps in the quality of education or differences in the trajectory of impaired cognitive function experienced by the two groups. Future investigations might take these findings into consideration for the design of studies evaluating black-white differences in dementia risk.

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Association between oxidative balance score and cardiovascular risk factors, aging, and incidence of dementia risk score: A prospective cohort study.

BackgroundOxidative stress is a key contributor to the pathogenesis of Alzheimer's disease and other dementias. The oxidative balance score (OBS), which reflects combined dietary and lifestyle exposure to pro-oxidant and antioxidant factors, serves as an integrated measure of oxidative stress burden.ObjectiveTo investigate the association between OBS and predicted late-life dementia risk using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score.MethodsWe analyzed data from 5088 participants aged 40-69 years without dementia at baseline from the Korean Genome and Epidemiology Study. Participants were categorized by OBS tertiles. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for developing a high risk of late-life dementia, defined by a CAIDE score &#x2265;8. Longitudinal changes in CAIDE scores were assessed using linear mixed-effects models.ResultsDuring a mean follow-up of 12.8 years, 1468 participants (28.9%) progressed to CAIDE-predicted high risk for late-life dementia. Compared with the lowest OBS tertile (T1), participants in the highest tertile (T3) had a significantly lower risk for developing high-risk late-life dementia (HR 0.74, 95% CI 0.65-0.84) and exhibited the lowest CAIDE scores (p&#x2009;<&#x2009;0.001). Each one-point increase in the OBS was associated with a 3% reduction in CAIDE-predicted dementia risk.ConclusionsA higher OBS was significantly associated with a lower predicted risk of late-life dementia. These findings suggest that maintaining an antioxidant-rich diet and a healthy lifestyle during midlife may be effective strategies for dementia prevention.

Alzheimer's disease↗

Postsecondary education and dementia risk in older Jesuit priests.

Lack of early childhood education has been implicated as a risk factor for dementia in late life. It is unclear whether dementia risk is also associated with less education in the adult years. The purpose of the present study was to determine whether amount of postsecondary education (i.e., education beyond the high school or 12th-grade level) is associated with dementia after age 60. Cognitive function (assessed by a neuropsychological test battery) and the prevalence of dementia (assessed by clinical criteria) were determined in 86 Jesuit priests (age 60 to 98) who had from 0 to 23 years of postsecondary education. Logistic regression was used to estimate the odds of dementia as a function of postsecondary education. The risk of dementia was increased in those with less postsecondary education (odds ratio = 3.4; 95% confidence interval, 1.2 to 10.0) after adjustment for age, IQ, and depression. These findings support an association between amount of postsecondary education and risk of dementia in late life.

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Proteomic signature of dementia risk in type 2 diabetes.

INTRODUCTION: Type 2 diabetes (T2D) significantly increases dementia risk, yet the molecular mechanisms underlying this association remain unclear. OBJECTIVES: This study aimed to identify protein signatures that distinguish dementia risk in T2D patients, develop a proteomic prediction model, and elucidate biological pathways connecting T2D and dementia. METHODS: We analyzed 2,920 plasma proteins from 52,958 participants (including 3,292 with T2D) in the UK Biobank Pharma Proteomics Project with a median follow-up of 14.6&#xa0;years. Cox regression models with interaction terms identified T2D-specific protein associations with dementia risk. Machine learning models were developed to predict dementia in T2D patients. Pathway analysis and weighted gene co-expression network analysis identified biological mechanisms linking T2D and dementia. RESULTS: We identified 471 proteins with significant interaction effects between T2D and dementia risk. In non-T2D individuals, elevated levels of neuronal pentraxin receptor (NPTXR, HR&#xa0;=&#xa0;0.74, 95&#xa0;%CI:0.66-0.83) and carbonic anhydrase 14 (CA14, HR&#xa0;=&#xa0;0.67, 95&#xa0;%CI:0.60-0.75) were exclusively associated with decreased dementia risk. Conversely, in T2D patients, elevated rho guanine nucleotide exchange factor 12 (ARHGEF12, HR&#xa0;=&#xa0;1.45, 95&#xa0;%CI:1.10-1.91) was specifically associated with increased dementia risk. A 51-protein model accurately predicted 15-year dementia risk in T2D patients (AUC&#xa0;=&#xa0;0.835, C-index&#xa0;=&#xa0;0.829), outperforming conventional clinical risk scores and maintaining high accuracy for Alzheimer's disease and vascular dementia. Pathway analysis revealed enrichment of IL6-JAK-STAT3 signaling in T2D-related dementia, while dysregulation of fatty acid metabolism was specific to T2D-associated Alzheimer's disease. CONCLUSIONS: This large-scale proteomic analysis identifies specific molecular signatures that differentiate dementia risk in diabetic and non-diabetic populations, with potential applications for early risk stratification and targeted interventions. The identified pathways provide novel insights into the pathophysiological processes connecting T2D and dementia and suggest potential therapeutic targets.

Humans↗

Risk score for the prediction of dementia risk in 20 years among middle aged people: a longitudinal, population-based study.

BACKGROUND: Several vascular risk factors are associated with dementia. We sought to develop a simple method for the prediction of the risk of late-life dementia in people of middle age on the basis of their risk profiles. METHODS: Data were used from the population-based CAIDE study, which included 1409 individuals who were studied in midlife and re-examined 20 years later for signs of dementia. Several midlife vascular risk factors were studied to create the scoring tool. The score values were estimated on the basis of beta coefficients and the dementia risk score was the sum of these individual scores (range 0-15). FINDINGS: Occurrence of dementia during the 20 years of follow-up was 4%. Future dementia was significantly predicted by high age (> or = 47 years), low education (< 10 years), hypertension, hypercholesterolaemia, and obesity. The dementia risk score predicted dementia well (area under curve 0.77; 95% CI 0.71-0.83). The risk of dementia according to the categories of the dementia risk score was 1.0% for those with a score of 0-5, 1.9% for a score of 6-7, 4.2% for a score of 8-9, 7.4% for a score of 10-11, and 16.4% for a score of 12-15. When the cut-off of 9 points or more was applied the sensitivity was 0.77, the specificity was 0.63, and the negative predictive value was 0.98. INTERPRETATION: The dementia risk score is a novel approach for the prediction of dementia risk, but should be validated and further improved to increase its predictive value. This approach highlights the role of vascular factors in the development of dementia and could help to identify individuals who might benefit from intensive lifestyle consultations and pharmacological interventions.

Area Under Curve↗

The effect of dementia risk factors on comparative and diagnostic selective reminding norms.

Robust comparative and diagnostic norms for the elderly are provided for the Selective Reminding Test (Buschke, 1973). Correcting for factors such as age and education level are appropriate for comparative norms, which are intended for ranking individuals with respect to their age and education matched peers. However, because age and education are both risk factors for dementia, correcting for these factors decreases test sensitivity for detecting dementia. Age- and education-corrected Selective Reminding scores have a sensitivity for detecting dementia that is 28% lower than uncorrected scores. Using information about age in combination with memory scores provided optimal discrimination of dementia. It is concluded that statistically removing the contribution of dementia risk factors from memory test scores can severely decrease discriminative validity for detecting dementia in the elderly.

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Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.

Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.

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Effects of hormone replacement therapy on cognitive aging and dementia risk in postmenopausal women: a review of ongoing large-scale, long-term clinical trials.

The aim of this review is to discuss the purpose, design, and expected findings of several ongoing large-scale, long-term clinical trials studying the effects of hormone replacement therapy (HRT) on cognitive aging and risk of developing dementia. The Women's Health Initiative Study of Cognitive Aging (WHISCA) and the cognitive component of the Women's International Study of long Duration Oestrogen after Menopause--Cognition (WISDOM-COG) (to be completed in 2005 and 2006, respectively) will provide information about the effects of HRT on cognitive aging. The Preventing Postmenopausal Memory Loss and Alzheimer's with Replacement Estrogens study (PREPARE), the Women's Health Initiative Memory Study (WHIMS) and the dementia component of WISDOM-COG (to be completed in 2003, 2005 and 2009, respectively) will address the question of whether estrogens can delay or prevent dementia. These ongoing clinical trials will also be the first to study the effects of estrogen with and without progesterone, and the effects of HRT in women with natural versus surgical menopause, on cognitive aging and risk of dementia. Based on the existing literature, we discuss which specific cognitive areas are most likely to be affected by HRT. We also raise the issue that the type of estrogen agent may affect the outcome of these studies.

Aging↗

Binge drinking in midlife and dementia risk.

BACKGROUND: Studies examining the long-term effects of alcohol consumption on cognitive functioning have produced conflicting results. Our goal was to determine whether a long follow-up period combined with information about drinking patterns, in addition to total alcohol consumption, would provide new insights about the relationship of alcohol use with dementia risk. METHODS: A population-based cohort of 554 Finnish twins, who had provided data on alcohol consumption in questionnaires in 1975 and 1981, was followed for 25 years. Subjects were age 65 years or older at the time of dementia assessment in 1999-2001. Dementia risk was analyzed with respect to varying patterns of alcohol use by log-linear modeling, adjusted for age, sex, and education. RESULTS: By the end of follow-up, 103 participants had developed dementia. Binge drinking (ie, alcohol exceeding the amount of 5 bottles of beer or a bottle of wine on 1 occasion at least monthly), as reported in 1975, was associated with a relative risk of 3.2 (95% confidence interval=1.2-8.6) for dementia. Passing out at least twice as a result of excessive alcohol use during the previous year, as reported in 1981, was associated with a relative risk of 10.5 (2.4-46) for dementia in drinkers. CONCLUSIONS: Binge drinking in midlife is associated with an increased risk of dementia.

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Mental, physical and social components in leisure activities equally contribute to decrease dementia risk.

BACKGROUND: There is accumulating evidence in the literature that leisure engagement has a beneficial effect on dementia. Most studies have grouped activities according to whether they were predominantly mental, physical or social. Since many activities contain more than one component, we aimed to verify the effect of all three major components on the dementia risk, as well as their combined effect. METHODS: A mental, social and physical component score was estimated for each activity by the researchers and a sample of elderly persons. The correlation between the ratings of the authors and the means of the elderly subjects' ratings was 0.86. The study population consisted of 776 nondemented subjects, aged 75 years and above, living in Stockholm, Sweden, who were still nondemented after 3 years and were followed for 3 more years to detect incident dementia cases. RESULTS: Multi-adjusted relative risks (RRs) of dementia for subjects with higher mental, physical and social component score sums were 0.71 (95% CI: 0.49-1.03), 0.61 (95% CI: 0.42-0.87) and 0.68 (95% CI: 0.47-0.99), respectively. The most beneficial effect was present for subjects with high scores in all or in two of the components (RR of dementia = 0.53; 95% CI: 0.36-0.78). CONCLUSIONS: These findings suggest that a broad spectrum of activities containing more than one of the components seems to be more beneficial than to be engaged in only one type of activity.

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"Brain Screen": A self-referral, screening program for strokes, falls and dementia risk factors.

BACKGROUND: Falls, strokes and dementia can be predicted and their occurrence can be delayed or even prevented by treatment of risk factors. The value of screening self-referred adults is unknown. OBJECTIVES: To assess whether a screening program of self-referred adults provides new and valuable medical information on risk factors for falls, stroke and dementia. METHOD: We examined 514 self-referred people (59% women, mean age 68+/-8 years (range 44-89) and 14+/-3 years of education) in our "Brain Screen" program. Participants completed detailed questionnaires and underwent a neurological examination, computerized gait analysis, carotid Duplex, serum lipid and homocysteine levels, a computerized neuropsychological battery (NeuroTrax) and the Mini-Mental State Exam. Information that was detected by "Brain Screen" was compared with the self-reported data. RESULTS: Unknown vascular risk factors detected by ""Brain Screen" included: high cholesterol in 44%, homocysteine > 10 micromol/L in 20%, >1 mm carotid intima-media thickness in 13%, and carotid narrowing (> 30%) in 2.2%. Unknown risk factors for falls were detected in 66% of the subjects who never fell. Of the 205 subjects (44%) who complained of memory decline, 28% had objective memory disturbances compared with their age group. Mild cognitive impairment (amnestic MCI) was clinically diagnosed in 17% of the population and dementia in 5%. CONCLUSION: Screening self-referred adults for falls, strokes and dementia risk factors detected significant unknown risk factors that can be treated in more than one-third of the participants. A national "Brain Screen" program can have significant impact on the health of the aging population.

Accidental Falls↗

[A study of associations between daily-social activity of elderly people living at home and symptoms of forgetfulness. Screening for dementia risk].

PURPOSE: Functional decrease in brain activity as a factor inducing dementia is due not only to aging but also to decrease in social exchange, loss of something to live for, and decrease in physical activity with indoor confinement. It might therefore be possible to use these parameters to screen for risk of dementia in community care programs. In the present study we evaluated the association between decreased daily-social activity and symptoms of forgetfulness. METHODS: The subjects were 6,486 people aged > or = 65 years living in 3 municipalities in Yamanashi Prefecture. A survey table concerning daily-social activity and symptoms of forgetfulness was produced, and a whole-sample survey was performed by mail. Cluster analysis of items such as symptoms of forgetfulness was performed, and clusters were obtained. Associations between these clusters and daily-social activity were then analyzed by the Mann-Whitney test. RESULTS: Of 5,556 replies (recovery rate, 85.7%), 3,067 with all items filled out (effective reply rate, 55.2%) were analyzed. None of the 21 items for forgetfulness was applicable in 600 of the subjects (19.6%). Cluster analysis of the other 2,467 subjects with 1 or more symptoms revealed the following 5 clusters: "common forgetfulness symptoms" consisting of 2 items, "decreased will to live" consisting of 8 items, "amnesic symptoms" consisting of 4 items, "emotional responses" consisting of 2 items, and "difficulty in daily life" consisting of 5 items. There were 31 types of cluster combinations in the subjects, and the most frequently applicable cluster was "common forgetfulness symptoms" (658 subjects, 21.5%). Comparison of the daily-social activity between the cluster groups showed significant differences in many of the items for daily-social activity with reference to the "decreased will to live". CONCLUSION: Among forgetfulness symptoms, items classified as related to "decreased will to live" were most associated with daily-social activity. This suggests utility for evaluation of daily-social activity, including intellectual and social activity frequency in elderly people in communities to select people for care programs for prevention of secondary dementia.

Activities of Daily Living↗

Abdominal aortic calcification on lateral spine images captured during bone density testing and late-life dementia risk in older women: A prospective cohort study.

BACKGROUND: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. METHODS: In prospective study of 958 ambulant community-dwelling older women (&#x2265;70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. FINDINGS: At baseline women were 75.0&#xa0;&#xb1;&#xa0;2.6 years, 44.7% had low AAC, 36.4% had moderate AAC and 18.9% had extensive AAC. Over 14.5- years, 150 (15.7%) women had a late-life dementia hospitalisation (n&#xa0;=&#xa0;132) and/or death (n&#xa0;=&#xa0;58). Compared to those with low AAC, women with moderate and extensive AAC were more likely to suffer late-life dementia hospitalisations (9.3%, 15.5%, 18.3%, respectively) and deaths (2.8%, 8.3%, 9.4%, respectively). After adjustment for cardiovascular risk factors and APOE, women with moderate and extensive AAC had twice the relative hazards of late-life dementia (moderate, aHR 2.03 95%CI 1.38-2.97; extensive, aHR 2.10 95%CI 1.33-3.32), compared to women with low AAC. INTERPRETATION: In community-dwelling older women, those with more advanced AAC had higher risk of late-life dementia, independent of cardiovascular risk factors and APOE genotype. Given the widespread use of bone density testing, simultaneously capturing AAC information may be a novel, non-invasive, scalable approach to identify older women at risk of late-life dementia. FUNDING: Kidney Health Australia, Healthway Health Promotion Foundation of Western Australia, Sir Charles Gairdner Hospital Research Advisory Committee Grant, National Health and Medical Research Council of Australia.

AAC, abdominal aortic calcification↗

Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS). METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician's assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4. RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28% (95% CI: 0.51 to 1.02), and AD by 41% (95% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect. CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

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Physical status and dementia risk: a three-year prospective study in urban Japan.

A three-year prospective study of 3,180 non-dementia persons in Sendai City, Japan was conducted to examine the effects of physical status and diseases diagnosed on dementia incidence. This cohort had been made at the initial survey in 1988 and the evaluation for incident dementia was performed on 2,461 respondents (77.4%) in a follow-up survey in 1991. Regarding physical status, the logistic regression including sex, age, health status, ambulatory activity and activities of daily living indicated that the poor health status and the limitation of ambulatory activity were significantly associated with an increased risk of dementia. The significant positive association with dementia was observed on stroke, respiratory disease and depression. This study identified the high risk population for dementia in the aspect of physical status.

Activities of Daily Living↗